OBJECTIVES: A. Overall objectives of Grant AM 17868. 1. To use gas chromatograph-mass spectrometry to define the biliary bile acid composition and characterize unusual bile acids in gallstone patients at the Mayo Clinic before and after treatment with chenodeoxycholic acid. 2. To use gas chromatography-mass spectrometry to measure plasma levels of bile acids by inverse isotope dilution employing deuterium-labeled bile acids. 3. To develop and validate new methods for bile acid kinetics with stable isotopes which are applicable to plasma samples. B. Goals for current year (1976): 1. Extension of gas chromatographic-mass spectrometric examination of biliary bile acids in gallstone patients; inclusion of four patients fed desoxycholic acid. 2. Synthesis of 3 Beta-2H labeled forms of lithocholic, deoxycholic, chenodeoxycholic ursodeoxycholic and cholic acids for internal standards in inverse isotope dilution measurements of plasma bile acids. 3. Determination of the detection limits for unlabeled bile acids in plasma as free, conjugated and conjugated-sulfated forms. 4. Synthesis of 13C labeled lithocholic, deoxycholic, chenodeoxycholic, ursodeoxycholic and cholic acid for further kinetic measurements and simultaneous measurement of all major bile acid turnover and synthesis rates. BIBLIOGRAPHIC REFERENCES: Szczepanik, P.A., D.L. Hachey and P. D. Klein: Characterization of bile acid methyl ester acetate derivatives using gas-liquid chromatography, electron impact and chemical ionization mass spectrometry. J. Lipid Research 17, 314-334 (1976). Hanson, R.F., G.C. Williams, D.L. Hachey and H.L. Sharp: Hepatic lesions and hemolysis following administration of 3-alpha, 7-alpha, 12-alpha-trihydroxy-5-Beta-cholestan-26-oyl taurine (Tauro-THCA) to rats. Gastroenterology 70, 983 (1976) Abstract.